The effects of diabetes on sympathetic neurovascular transmission

© 2013 Dr. Niloufer Jahan JohansenImpaired neural control of arteries is implicated in the etiology of diabetic foot, a major complication of diabetes. The loss of sympathetic nerve-mediated control of blood flow to plantar skin may be an early change that contributes to the later development of microvascular disease in foot skin. The mechanisms that modify sympathetic regulation of arterial vessels are not understood, but are suggested to be due to diabetes-induced neuropathy. Therefore the primary aim of this thesis was to investigate the effects of diabetes on the sympathetic innervation and activation of plantar metatarsal arteries (PMAs) that supply blood to plantar skin of the hind paw digits in rats. The streptozotocin (STZ) rat model of type I diabetes was chosen as it has been widely used to investigate mechanisms that lead to diabetic complications. Eight-week-old male Wistar rats were treated with STZ (60 mg/kg i.p.) or vehicle (citrate-buffer i.p.; controls). STZ-treated rats received no insulin (STZ-NI) or were treated with a low (~1 unit/day; STZ-LI) or a high (~4 units/day; STZ-HI) dose of insulin. The STZ-NI and STZ-LI rats were hyperglycemic (blood glucose >20 mM), whereas STZ-HI rats were normoglycemic (blood glucose